Department of Neurology, School of Medicine, Koç University, İstanbul, Turkey.
Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory, KUTTAM, School of Medicine, Koç University, İstanbul, Turkey.
Mov Disord. 2021 Jul;36(7):1676-1688. doi: 10.1002/mds.28518. Epub 2021 Feb 24.
The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations.
To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population.
Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype.
Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data.
With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.
遗传性共济失调的遗传和流行病学特征已在多个群体中报道；然而，土耳其仍未被探索。由于高近亲结婚率，隐性共济失调在土耳其比在西欧人群中更为常见。
确定遗传性共济失调在土耳其人群中的流行率和遗传结构。
我们的队列包括 1296 名索引病例和 324 名受影响的家族成员。对具有显性遗传模式的家族中的三核苷酸重复扩增以及散发性病例进行聚合酶链反应（PCR）后 Sanger 测序或片段分析。在所有常染色体隐性病例和表型相符的散发性病例中检测铁蛋白（FXN）基因的扩增。对 251 名基于家族史、发病年龄和表型选择的先证者进行全外显子组测序。
在 1296 名先证者中的 30%中发现了已知共济失调基因的突变。弗里德赖希共济失调是土耳其最常见的隐性共济失调，其次是沙格奈-谢格奈的常染色体隐性痉挛性共济失调。脊髓小脑性共济失调 2 型和 1 型是最常见的显性共济失调。对 251 名先证者进行了全外显子组测序，诊断率约为 50%。在众多基因中发现了 48 种新的变体，表明存在高度异质性。根据临床数据讨论了意义不明的变体。
通过在全国范围内招募的大样本量，我们认为我们的结果提供了土耳其遗传性共济失调频率的准确图片。© 2021 国际帕金森病和运动障碍学会。
